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The extracellular matrix (ECM) is present in all solid tissues and is a master regulator of cell behavior and phenotype. The ECM in each tissue is characterized by its biochemical and biophysical properties, which are modified in many different types of disease, especially cancer. Hyaluronic acid (HA), as a biopolymer, has emerged as a remarkable ECM component by its viscoelastic properties, its hygroscopic capacities and the diversity of cell processes it controls in health and disease.
BIOMIMESYS®, a patented HA-based hydroscaffold, is a highly reproducible and physiological matrix that is suitable for long-term 3D cell culture. Using BIOMIMESYS® Oncology - made of HA biofunctionalized with undenaturated collagen I - we investigated the influence of (i) matrix composition (with/without laminin) and (ii) stiffness on the growth and expression of CD44 (a receptor of HA) in spheroids made of breast cancer cell lines (MCF7, MDA-MB-231) and normal cells (MCF10A) along time. Analyses were carried out using high content analysis/screening (HCA/HCS, high throughput confocal microscopy).
As a whole, the results showed that the cell growth was lowered in the presence of laminin but promoted with increased stiffness. Except for MCF10A cells, the expression of CD44 had the tendency to increase over time, while the stiffness and the presence of laminin had no significant impact on its expression. Given that BIOMIMESYS® is a highly defined and easily tunable matrix, this physiological 3D cell culture system allows to study the impact of biochemical and biophysical properties of the matrix.
By better mimicking the cancer microenvironment - including the ECM - the new generation of 3D cell culture systems might help to discover new effective anti-cancer therapies. In this frame, our aim is to study the response of cancer cells in BIOMIMESYS® to a large set of anti-tumor molecules, using our HCS platform.
Keywords: 3D cell culture, hyaluronic acid, breast cancer, stiffness, high content screening